The present invention relates to a process for the preparation of an oxazolidinecarboxylic acid or derivatives thereof, of general formula: 
from an acid or derivatives thereof, of general formula: 
In the formulae (I) and (II),
Rxe2x80x2 represents a hydrogen atom or an alkali metal or alkaline-earth metal atom or an alkyl radical containing 1 to 4 carbon atoms optionally substituted with a phenyl radical,
R1 represents a benzoyl radical or a radical R2xe2x80x94Oxe2x80x94COxe2x80x94 in which R2 represents:
a straight or branched alkyl radical containing 1 to 8 carbon atoms, an alkenyl radical containing 3 to 6 carbon atoms, a cycloalkyl radical containing 3 to 6 carbon atoms or a cycloalkenyl radical containing 4 to 6 carbon atoms, these radicals being optionally substituted with one or more substituents chosen from halogen atoms and hydroxyl radicals, alkyloxy radicals containing 1 to 4 carbon atoms, dialkylamino radicals in which each alkyl portion contains 1 to 4 carbon atoms, piperidino, morpholino and 1-piperazinyl (optionally substituted at position 4 with an alkyl radical containing 1 to 4 carbon atoms or with a phenylalkyl radical in which the alkyl portion contains 1 to 4 carbon atoms) radicals, cycloalkyl radicals containing 4 to 6 carbon atoms, alkenyl radicals containing 4 to 6 carbon atoms, phenyl, cyano and carboxyl radicals or alkyloxycarbonyl radicals in which the alkyl portion contains 1 to 4 carbon atoms,
or a phenyl radical optionally substituted with one or more atoms or radicals chosen from halogen atoms and alkyl radicals containing 1 to 4 carbon atoms or alkyloxy radicals containing 1 to 4 carbon atoms,
or a saturated or unsaturated nitrogen-containing 5- or 6-membered heterocyclic radical optionally substituted with one or more alkyl radicals containing 1 to 4 carbon atoms,
R3 and R4, which may be identical or different, represent a hydrogen atom or an alkyl radical containing 1 to 4 carbon atoms or an aralkyl radical in which the alkyl portion contains 1 to 4 carbon atoms and the aryl portion preferably represents a phenyl radical optionally substituted with one or more alkoxy radicals containing 1 to 4 carbon atoms, or an aryl radical preferably a phenyl radical optionally substituted with one or more alkoxy radicals containing 1 to 4 carbon atoms, or alternatively R3 represents an alkoxy radical containing 1 to 4 carbon atoms or a trihalomethyl radical such as trichloromethyl or a phenyl radical. substituted with a trihalomethyl radical such as trichloromethyl and R4 represents a hydrogen atom, or alternatively R3 and R4 form, together with the carbon atom to which they are attached, a 4- to 7-membered ring.
The acid of general formula (I) is particularly useful for preparing the therapeutically active taxoids of general formula: 
in which:
R represents a hydrogen atom or the acetyl radical,
R1 is defined as above, and
R5 represents an iodine atom or an alkenyl radical containing 2 to 8 carbon atoms optionally substituted with a phenyl radical, an alkynyl radical containing 2 carbon atoms or a phenyl, formyl, alkanoyl, aroyl, hydroxymethyl, carboxyl or alkoxycarbonyl radical.
According to Application PCT WO 9209589, the preparation of a product of general formula (III) requires the use of an oxazolidinecarboxylic acid of general formula: 
in which R5 is defined as above, Rxe2x80x23 and Rxe2x80x24, which may be identical or different, represent an alkyl radical containing 1 to 4 carbon atoms optionally substituted with one or more aryl (phenyl) radicals or represent an aryl (phenyl) radical, or alternatively Rxe2x80x23 and Rxe2x80x24 form, together with the carbon atom to which they are attached, a 4- to 7-membered ring, and Boc represents the t-butoxycarbonyl radical, which is obtained from an aldehyde of general formula: 
in which R5 is defined as above, which, depending on the meanings of R5, is not always easily accessible.
According to the invention, the product of general formula (I) in which Rxe2x80x2 represents an alkyl radical optionally substituted with a phenyl radical is obtained by iodination, according to the usual methods, of a product of general formula (II) in which Rxe2x80x2 represents an alkyl radical optionally substituted with a phenyl radical.
The iodination may generally be carried out either using iodine in the presence of bis(trifluoroacetoxy)iodobenzene by working in an organic solvent such as a halogenated aliphatic hydrocarbon like dichloromethane at a temperature between 0 and 50xc2x0 C., or alternatively by the action of iodine in the presence of ammonium cerium nitrate in acetic acid or methanol, or alternatively by the action of iodine in the presence of silver trifluoroacetate, or alternatively by the action of N-iodosuccinimide in the presence of hydroxy(tosyloxy)iodobenzene (Koser""s reagent) in methanol, or alternatively by the action of benzyltrimethylammonium dichloroiodide in the presence of zinc chloride in acetic acid.
The product of general formula (I) for which Rxe2x80x2 represents a hydrogen atom may be obtained by saponification of a product of general formula (I) in which Rxe2x80x2 represents an alkyl radical optionally substituted with a phenyl radical.
The product of general formula (II) in which Rxe2x80x2 represents an alkyl radical optionally substituted with a phenyl radical, R3 and R4 are defined as above, may be obtained by reacting a product of general formula: 
in which R3 and R4 are defined as above in the form of a dialkyl acetyl or an alkyl enol ether, with an ester of general formula: 
in which R1 and Rxe2x80x2 are defined as above, which may be obtained under the conditions described in the Application PCT WO 9209589, corresponding U.S. Pat. No. 5,476,954.
The product of general formula (I) may be converted to a product of general formula (III) according to one of the following methods:
1) after replacing the iodine atom of the product of general formula (I), in which Rxe2x80x2 represents an alkyl radical optionally substituted with a phenyl radical, with an alkenyl radical containing 2 to 8 carbon atoms optionally substituted with a phenyl radical, an alkynyl radical containing 2 carbon atoms or a phenyl, formyl, alkanoyl, aroyl, hydroxymethyl, carboxyl or alkoxycarbonyl radical according to the known methods, and saponification, the product obtained of general formula: 
xe2x80x83in which R1, R3 and R4 are defined as above, and Rxe2x80x25 represents an alkenyl radical optionally substituted with a phenyl radical or an alkynyl, phenyl, alkanoyl, aroyl, formyl, hydroxymethyl, carboxyl or alkoxycarbonyl radical, or a derivative of the acid of general formula (VIII), is condensed with a protected baccatin III of general formula: 
xe2x80x83in which G1 represents a protecting group for the hydroxyl function and G2 represents an acetyl radical or a protecting group for the hydroxyl function, in order to obtain a product of general formula: 
xe2x80x83in which R1, R3, R4, Rxe2x80x25, G1 and G2 are defined as above, in which the protecting groups represented by G1 and G2 are replaced by hydrogen atoms by passing, depending on the meanings of R3 and R4, via an intermediate product of general formula: 
xe2x80x83in which Rxe2x80x25 is defined as above, Gxe2x80x21 represents a hydrogen atom or a protecting group for the hydroxyl function and Gxe2x80x22 represents a hydrogen atom or an acetyl radical or a protecting group for the hydroxyl function, in which the amine function is acylated before replacing the protecting groups Gxe2x80x21 and, where appropriate, Gxe2x80x22 by hydrogen atoms.
2) the product of general formula (I), in which Rxe2x80x2 represents a hydrogen atom, is condensed with a protected baccatin III of general formula (IX) in order to give a product of general formula: 
xe2x80x83in which R1, R3, R4, G1 and G2 are defined as above, in which the protecting groups represented by G1 and G2 are replaced by hydrogen atoms by passing, depending on the meanings of R3 and R4, via an intermediate product of general formula: 
xe2x80x83in which Gxe2x80x21 and Gxe2x80x22 are defined as above, in which the amine function is acylated before replacing the groups Gxe2x80x21 and, where appropriate, Gxe2x80x22 by hydrogen atoms and then the iodine atom by a radical Rxe2x80x25 as defined above.
3) a product of general formula (III) may also be obtained from a product of general formula (III) prepared according to the sequence described above in 1) by any method which allows a substituent Rxe2x80x25 to be converted into a different substituent Rxe2x80x25, for example, a product of general formula (III) in which Rxe2x80x25 represents a vinyl radical may be converted, by ozonolysis, to a different product of general formula (III) in which Rxe2x80x25 represents a formyl radical.
Depending on the meanings of Rxe2x80x25, the product of general formula (VIII), in ester form, may be prepared according to known methods.
The product of general formula (VIII), in ester form, for which Rxe2x80x25 represents an alkenyl radical optionally substituted with a phenyl radical, may be obtained by reacting a boronic acid of general formula: 
in which Rxe2x80x25 is defined as above, with a product of general formula (I) in which Rxe2x80x2 represents an alkyl radical optionally substituted with a phenyl radical.
The reaction is generally carried out in the presence of a catalyst such as palladium combined with a ligand such as triphenylphosphine by working in an organic solvent such as an aromatic hydrocarbon (benzene, toluene or xylene) at a temperature between 0 and 100xc2x0 C.
The product of general formula (VIII), in ester form, for which Rxe2x80x25 represents an alkynyl radical, may be obtained by reacting an acetylene derivative of general formula:
xe2x80x83Hxe2x80x94Cxe2x89xa1Cxe2x80x94Si(Rxe2x80x3)3xe2x80x83xe2x80x83(XV)
in which Rxe2x80x3 represents an alkyl radical containing 1 to 4 carbon atoms, with a product of general formula (I) in which Rxe2x80x2 represents an alkyl radical optionally substituted with a phenyl radical.
The reaction is generally first of all carried out in the presence of a catalyst consisting of palladium combined with a ligand such as triphenylphosphine and a copper salt such as cuprous iodide, by working in a basic organic solvent such as diethylamine at a temperature in the region of 20xc2x0 C., and then in the presence of a desilylating agent such as silver nitrate in a protic solvent or of silver nitrate in an organic solvent such as an aliphatic alcohol like ethanol, in order to displace the silyl residue.
The product of general formula (VIII), in ester form, for which Rxe2x80x25 represents a formyl, acyl or aroyl radical, may be obtained by ozonolysis of a product of general formula (VIII), in ester form, in which Rxe2x80x25 represents an alkenyl radical optionally substituted with a phenyl radical.
The ozonolysis is generally carried out in an organic solvent such as a dichloromethane/methanol mixture at a temperature lower than xe2x88x9250xc2x0 C.
The product of general formula (VIII), in ester form, for which Rxe2x80x25 represents a hydroxymethyl radical, may be obtained by reduction, using an alkali metal cyanoborohydride, of a product of general formula (VIII) for which Rxe2x80x25 represents a formyl radical.
The product of general formula (VIII), in ester form, for which Rxe2x80x25 represents a carboxyl radical, may be obtained by oxidation, for example using sodium perborate, of a product of general formula (VIII) in which Rxe2x80x25 represents a formyl radical.
The product of general formula (VIII), in ester form, for which Rxe2x80x25 represents an alkoxycarbonyl radical, may be obtained, for example, by reacting an N,N-dimethylformamide acetal with a product of general formula (VIII) in which Rxe2x80x25 represents a carboxyl radical.
The saponification of a product of general formula (I) or of a product of general formula (VIII), in ester form, in which Rxe2x80x2 represents an alkyl radical optionally substituted with a phenyl radical, to a product of general formula (I) or a product of general formula (VIII), in which Rxe2x80x2 represents a hydrogen atom, may be carried out using an inorganic base such as lithium hydroxide, by working in an aqueous-alcoholic medium such as a water/methanol mixture.
When, in the product of general formula (III), R5 represents an iodine atom, its replacement by a radical Rxe2x80x25, is carried out under the conditions described above, in order to convert a product of general formula (I) to a product of general formula (VIII)
The esterification of the protected baccatin III using an acid of general formula (I) or an acid of general formula (VIII) or a derivative such as a halide, an anhydride or a mixed anhydride may be carried out under the following conditions:
1) esterification using an acid of general formula (I) or (VIII) may be carried out in the presence of a condensing agent (carbodiimide, reactive carbonate) and an activating agent (amino pyridine) in an organic solvent (ethers, esters, ketones, nitrites, aliphatic hydrocarbons, halogenated aliphatic hydrocarbons, aromatic hydrocarbons) at a temperature between xe2x88x9210 and 90xc2x0 C.
2) esterification may also be performed by using the acid of general formula (I) or (VIII) in anhydride form in the presence of an activating agent (aminopyridine) in an organic solvent (ethers, esters, ketones, nitriles, aliphatic hydrocarbons, halogenated aliphatic hydrocarbons, aromatic hydrocarbons) at a temperature between 0 and 90xc2x0 C.
3) esterification may also be performed by using the acid of general formula (I) or (VIII) in halide form or in an anhydride form with an aliphatic or aromatic acid, optionally prepared in situ, in the presence of a base (tertiary aliphatic amine) by working in an organic solvent (ethers, esters, ketones, nitriles, aliphatic hydrocarbons, halogenated aliphatic hydrocarbons, aromatic hydrocarbons) at a temperature between 0 and 80xc2x0 C.
Replacement of the protecting groups R3, R4, G1 and G2 in the products of general formulae (X) or (XII) by hydrogen atoms may be carried out by working, depending on the meanings of R3 and R4, in the following way:
1) when R3 represents a hydrogen atom or an alkoxy radical containing 1 to 4 carbon atoms or an optionally substituted aryl radical and R4 represents a hydrogen atom, the product of general formula (X) or (XII) is treated in an acidic medium in order to obtain a product of general formula: 
xe2x80x83in which R1 and R5 are defined as above, Gxe2x80x21 represents a hydrogen atom or a protecting group for the hydroxyl function and Gxe2x80x22 represents a hydrogen atom or an acetyl radical or a protecting group for the hydroxyl function, in which the protecting groups Gxe2x80x21 and Gxe2x80x22 are, if necessary, replaced by hydrogen atoms in order to obtain a product of general formula (III).
The deprotection of the side chain of the product of general formula (X) or (XII) may be carried out in the presence of an inorganic acid (hydrochloric acid or sulphuric acid) or an organic acid (acetic acid, methanesulphonic acid, trifluoromethanesulphonic acid or p-toluenesulphonic acid), used alone or mixed, by working in an organic solvent chosen from alcohols (methanol, ethanol or isopropanol), ethers (tetrahydrofuran, diisopropyl ether or methyl t-butyl ether), esters (ethyl acetate, isopropyl acetate or n-butyl acetate), aliphatic hydrocarbons (pentane, hexane or heptane), halogenated aliphatic hydrocarbons (dichloromethane or 1,2-dichloroethane), aromatic hydrocarbons (benzene, toluene or xylenes) and nitriles (acetonitrile) at a temperature between xe2x88x9210 and 60xc2x0 C., preferably between 15 and 30xc2x0 C. The acid may be used in a catalytic or stoichiometric amount or in excess.
The deprotection may also be performed under oxidizing conditions by using, for example, ammonium cerium IV nitrate in an acetone/water mixture or 2,3-dichloro-5,6-dicyano-1,4-benzoquinone in water.
The deprotection may also be performed under reducing conditions, for example by hydrogenolysis in the presence of a catalyst.
The radicals G1 and G2, as well as Gxe2x80x21 and Gxe2x80x22, when they represent a protecting group for the hydroxyl function, are preferably 2,2,2-trichloroethoxycarbonyl or 2-(2-trichloromethylpropoxy)carbonyl radicals or trialkylsilyl, dialkylarylsilyl, alkyldiarylsilyl or triarylsilyl radicals in which the alkyl portions contain 1 to 4 carbon atoms and the aryl portions are preferably phenyl radicals.
Replacement by hydrogen atoms, in the product of general formula (XVI) of the protecting groups Gxe2x80x21 and, where appropriate, Gxe2x80x22 representing a silyl radical, may be carried out simultaneously with the deprotection of the side chain.
The replacement by hydrogen atoms, in the product of general formula (XVI), of the protecting groups Gxe2x80x21 and Gxe2x80x22 representing a 2,2,2-trichloroethoxycarbonyl or 2-(2-trichloromethylpropoxy)carbonyl radical, is carried out by zinc, optionally combined with copper, in the presence of acetic acid at a temperature between 20 and 60xc2x0 C., or using an inorganic or organic acid such as hydrochloric acid or acetic acid dissolved in an aliphatic alcohol containing 1 to 3 carbon atoms or in an aliphatic ester such as ethyl acetate, isopropyl acetate or n-butyl acetate in the presence of zinc optionally combined with copper,
2) when R1 represents a t-butoxycarbonyl radical, R3 and R4, which may be identical or different, represent an alkyl radical containing 1 to 4 carbon atoms or an aralkyl radical in which the alkyl portion contains 1 to 4 carbon atoms and the aryl portion is preferably an optionally substituted phenyl radical or an aryl, preferably phenyl, radical, or alternatively R3 represents a trihalomethyl radical or a phenyl radical substituted with a trihalomethyl radical and R4 represents a hydrogen atom, or alternatively R3 and R4 form, together with the carbon atom to which they are attached, a 4- to 7-membered ring, the product of general formula (X) or (XII) is converted in acidic medium to a product of general formula (XI) or (XIII), which is acylated using benzoyl chloride or a reactive derivative of general formula:
R2xe2x80x94Oxe2x80x94COxe2x80x94Xxe2x80x83xe2x80x83(XVII)
xe2x80x83in which R2 is defined as above and X represents a halogen atom (fluorine or chlorine) or a residue xe2x80x94Oxe2x80x94R2 or xe2x80x94Oxe2x80x94COxe2x80x94Oxe2x80x94R2, in order to obtain a product of general formula (XVI) in which the protecting groups Gxe2x80x21 and, where appropriate, Gxe2x80x22 are replaced, if necessary by hydrogen atoms in order to obtain a product of general formula (III).
The products of general formula (XI) or (XIII), in which Gxe2x80x21 represents a protecting group for the hydroxyl function chosen from 2,2,2-trichloroethoxycarbonyl and 2-(2-trichloromethylpropoxy)carbonyl radicals and Gxe2x80x22 represents an acetyl radical or a protecting group for the hydroxyl function chosen from 2,2,2-trichloroethoxycarbonyl and 2-(2-trichloromethylpropoxy)carbonyl radicals, may be obtained by treating a product of general formula (X) or (XII), in which R1, G1 and G2 are defined as above, R3 and R4, which may be identical or different, represent an alkyl, aralkyl or aryl radical, or alternatively R3 and R4 form, together with the carbon atom to which they are attached, a 4- to 7-membered ring, with an inorganic acid (hydrochloric acid or sulphuric acid) or an organic acid (formic acid) optionally in an alcohol containing 1 to 3 carbon atoms (methanol, ethanol or isopropanol), at a temperature between 0 and 50xc2x0 C. Preferably, formic acid is used at a temperature in the region of 20xc2x0 C.
The products of general formula (XI) or (XIII), in which Gxe2x80x21 represents a hydrogen atom and Gxe2x80x22 represents an acetyl radical, may be obtained by treating a product of general formula (X) or (XII), in which G1 represents a silyl radical and G2 represents an acetyl radical, R3 and R4, which may be identical or different, represent an alkyl, aralkyl or aryl radical, or alternatively R3 and R4 form, together with the carbon atom to which they are attached, a 4- to 7-membered ring, with an inorganic acid (hydrochloric acid, sulphuric acid or hydrofluoric acid) or an organic acid (formic acid, acetic acid, methanesulphonic acid, trifluoromethanesulphonic acid or p-toluenesulphonic acid) used alone or mixed, by working in an organic solvent chosen from alcohols, ethers, esters, aliphatic hydrocarbons, halogenated aliphatic hydrocarbons, aromatic hydrocarbons or nitriles at a temperature between xe2x88x9210 and 60xc2x0 C.
The products of general formula (XI) or (XIII), in which Gxe2x80x21 represents a hydrogen atom and Gxe2x80x22 represents a hydrogen atom or an acetyl radical, may be obtained by treating a product of general formula (X) or (XII), in which G1 represents a protecting group chosen from 2,2,2-trichloroethoxycarbonyl or 2-(2-trichloromethylpropoxy)carbonyl radicals, G2 represents an acetyl radical or a protecting group chosen from 2,2,2-trichloroethoxycarbonyl or 2-(2-trichloromethylpropoxy)carbonyl radicals, R3 represents a trihalomethyl radical or a phenyl radical substituted with a trihalomethyl radical and R4 represents a hydrogen atom, with zinc, optionally combined with copper, in the presence of acetic acid at a temperature between 30 and 60xc2x0 C., or using an inorganic or organic acid such as hydrochloric acid or acetic acid dissolved in an aliphatic alcohol containing 1 to 3 carbon atoms (methanol, ethanol, propanol or isopropanol) or in an aliphatic ester (ethyl acetate, isopropyl acetate or n-butyl acetate) in the presence of zinc optionally combined with copper.
Acylation of the product of general formula (XI) or (XIII) using benzoyl chloride or a reactive derivative of general formula (XVII) is carried out in an inert organic solvent chosen from esters such as ethyl acetate, isopropyl acetate or n-butyl acetate and halogenated aliphatic hydrocarbons such as dichloromethane or 1,2-dichloroethane in the presence of an inorganic base such as sodium bicarbonate or an organic base such as triethylamine. The reaction is carried out at a temperature between 0 and 50xc2x0 C., preferably in the region of 20xc2x0 C.
The possible replacement by hydrogen atoms of the protecting groups Gxe2x80x21 and Gxe2x80x22 in the product of general formula (XVI), when they represent a 2,2,2-trichloroethoxycarbonyl or 2-(2-trichloromethylpropoxy)carbonyl radical, is generally carried out by treatment with zinc, optionally combined with copper, in the presence of acetic acid at a temperature between 30 and 60xc2x0 C., or using an inorganic or organic acid such as hydrochloric acid or acetic acid dissolved in an aliphatic alcohol containing 1 to 3 carbon atoms (methanol, ethanol or isopropanol) or in an aliphatic ester (ethyl acetate, isopropyl acetate or n-butyl is acetate) in the presence of zinc optionally combined with copper.